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Abstract Background Refsum disease is a rare autosomal recessive hereditary disorder of lipid metabolism that results in the accumulation of phytanic acid. This syndrome is characterized with a range of classic symptoms including ataxia, peripheral neuropathy, amyotrophy, retinopathy, ichthyosis, and hearing loss. Later in life, individuals with Refsum disease may present cardiac manifestations, such as arrhythmias or conduction defects (first-degree atrioventricular block and bundle branch block) and hypertrophic or dilated cardiomyopathy, leading to heart failure and sudden death. To the best of our knowledge, this is the first case revealed by cardiac manifestations described in literature. Case presentation: We report the case of 38-year-old white Moroccan male who was admitted in our department for an acute decompensated heart failure episode. Transthoracic echocardiography found a dilated cardiomyopathy with a reduced ejection fraction at 15%. Further evaluation showed different features of Refsum disease. High plasma level of phytanic acid confirmed the diagnosis. Cardiac manifestations are frequent in the late course of the adult Refsum disease and include, cardiomyopathy, electrical abnormalities, and sudden cardiac death. Moreover, arrhythmias remain one of the main causes of death in these patients. Conclusion Refsum’s disease is an autosomal recessive disorder. It presents as retinitis pigmentosa with anosmia, deafness ataxia, and cardiac defects. Current interventions for individuals with Refsum disease consist of dietary phytanic acid restriction and lipid apheresis to control symptoms and enhance quality of life.

Background: Refsum disease is a rare autosomal recessive hereditary disorder of lipid metabolism that results in the accumulation of phytanic acid. This syndrome is characterized with a range of classic symptoms including ataxia, peripheral neuropathy, amyotrophy, retinopathy, ichthyosis, and hearing loss. Later in life, individuals with Refsum disease may present cardiac manifestations, such as arrhythmias or conduction defects (first-degree atrioventricular block and bundle branch block) and hypertrophic or dilated cardiomyopathy, leading to heart failure and sudden death. To the best of our knowledge, this is the first case revealed by cardiac manifestations described in literature. Case presentation: We report the case of 38-year-old white Moroccan male who was admitted in our department for an acute decompensated heart failure episode. Transthoracic echocardiography found a dilated cardiomyopathy with a reduced ejection fraction at 15%. Further evaluation showed different features of Refsum disease. High plasma level of phytanic acid confirmed the diagnosis. Cardiac manifestations are frequent in the late course of the adult Refsum disease and include, cardiomyopathy, electrical abnormalities, and sudden cardiac death. Moreover, arrhythmias remain one of the main causes of death in these patients. Conclusion: Refsum's disease is an autosomal recessive disorder. It presents as retinitis pigmentosa with anosmia, deafness ataxia, and cardiac defects. Current interventions for individuals with Refsum disease consist of dietary phytanic acid restriction and lipid apheresis to control symptoms and enhance quality of life. [ABSTRACT FROM AUTHOR]

PurposeTo illustrate the importance of systemic evaluation in retinal dystrophies through examples of Alstrom syndrome, Bardet Biedl syndrome, and Refsum disease.ObservationsDetailed eye evaluations, including visual acuity, visual field, slit lamp examination, and indirect ophthalmoscopy were performed. Retinal imaging included fundus photography and spectral domain optical coherence tomography (SD-OCT). Functional testing of the retina was done using full field electroretinography (ffERG). In addition, molecular genetic testing was performed using a ciliopathy panel, a retinal dystrophy panel, and whole genome sequencing (WGS).We report three individuals who presented with vision concerns first to ophthalmology, noted to have retinal dystrophy, and then referred to genomic medicine for genetic testing. Additional evaluation led to suspicion of specific groups of systemic disorders and guided appropriate genetic testing. The first individual presented with retinal dystrophy, obesity, and short stature with no reported neurocognitive deficits. Genetic testing included a ciliopathy panel that was negative followed by WGS that identified biallelic variants in ALMS: a novel frame-shift pathogenic variant c.6525dupT (p.Gln2176Serfs*17) and a rare nonsense pathogenic variant c.2035C > T (p.Arg679Ter) consistent with Alstrom syndrome. The second individual presented with retinal dystrophy, central obesity, and mild neurocognitive deficits. A ciliopathy genetic testing panel identified a homozygous pathogenic variant in BBS7: c.389_390del (p.Asn130Thrfs*4), confirming the diagnosis of Bardet Biedl syndrome. The third individual presented with progressive vision loss due to retinitis pigmentosa, anosmia, hearing loss, and shortened metatarsals and digits. Genetic testing identified two variants in PHYH: c.375_375del (p.Glu126Argfs*2) a pathogenic variant and c.536A > G (p.His179Arg), a variant of uncertain significance (VUS), suggestive of Refsum disease. Additional biochemical testing revealed markedly elevated phytanic acid with a low concentration of pristanic acid and normal concentrations of very long-chain fatty acids (C22:0, C24:0, C26:0), a pattern consistent with a diagnosis of Refsum disease.Conclusions and importanceIn individuals who present with retinal dystrophy to ophthalmologists, additional systemic manifestations such as sensorineural hearing loss, anosmia, or polydactyly, should be sought and a positive history or examination finding should prompt an immediate referral to a clinical geneticist for additional evaluation and appropriate genetic testing. This facilitates pre-test genetic counseling and allows for more accurate diagnosis, prognosis, and management of affected individuals along with better recurrence risk estimates for family members. Identification of an underlying etiology also enhances the understanding of the pathophysiology of disease and expands the genotypic and phenotypic spectrum. Ultimately, successful recognition of these diseases facilitates development of targeted therapies and surveillance of affected individuals.

Individuals with Hereditary Motor and Sensory Neuropathy (HMSN) are commonly provided with orthopedic footwear to improve gait. Although orthopedic footwear has shown to improve walking speed and spatiotemporal parameters, its effect on gait adaptability has not been established. What is the effect of orthopedic footwear on gait adaptability in individuals with HMSN? Fifteen individuals with HMSN performed a precision stepping task on an instrumented treadmill projecting visual targets, while wearing either custom-made orthopedic or standardized footwear (i.e. minimally supportive, flexible sneakers). Primary measure of gait adaptability was the absolute Euclidean distance [mm] between the target center and the middle of the foot (absolute error). Secondary outcomes included the relative and variable error [mm] in both anterior-posterior (AP) and medial-lateral (ML) directions. Dynamic balance was assessed by the prediction of ML foot placement based on the ML center of mass position and velocity, using linear regression. Dynamic balance was primarily determined by foot placement deviation in terms of root mean square error. Another aspect of dynamic balance was foot placement adherence in terms of the coefficient of determination (R2). Differences between the footwear conditions were analyzed with a paired t-test or Wilcoxon signed-rank test (α = 0.05). The absolute error, relative error (AP) and variable error (AP and ML) decreased with orthopedic footwear, whereas the relative error in ML-direction slightly increased. As for dynamic balance, no effect on foot placement deviation or adherence was found. Gait adaptability improved with orthopedic compared to standardized footwear in people with HMSN, as indicated by improved precision stepping. Dynamic balance, as a possible underlying mechanism, was not affected by orthopedic footwear. • Orthopedic footwear improves gait in individuals with HMSN. • Effect on gait adaptability has not been established. • Comparison between orthopedic footwear and minimally supportive, flexible sneakers. • Orthopedic footwear improved gait adaptability. • Dynamic balance, as underlying mechanism, was not affected. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the characteristics of the spread of hereditary motor and sensory neuropathy type 1A in the Sumy region, in terms of administrative units and specific ethnic groups of the population. Materials and methods. An epidemiological study of hereditary motor and sensory neuropathy (HMSN) type 1A in the Sumy region was conducted based on patient referrals to various healthcare facilities from 2014 to 2017. The prevalence of HMSN in the Sumy region was studied using an epidemiological approach. The prevalence rate of HMSN was calculated for different administrative units of the Sumy region, as well as for specific ethnic groups of the population. Results. The study registered 67 patients with hereditary motor and sensory neuropathy type 1A in the Sumy region. The prevalence rate of hereditary motor and sensory neuropathy type 1A in the Sumy region was 5.96 per 100,000 population. Of the HMSN patients, 47.8 % (32 individuals) resided in urban areas, while 52.2 % (35 individuals) lived in rural areas. In terms of gender distribution, 59.7 % (40 individuals) were female, and 40.3 % (27 individuals) were male. Most patients were of Ukrainian ethnicity (77.6 %), followed by Russians (20.9 %). Belarusians accounted for 1.5 % of HMSN patients in the Sumy region. Among other ethnic groups present in the Sumy region, HMSN type 1A was not detected. Conclusions. Hereditary motor and sensory neuropathy type 1A is unevenly distributed in the Sumy region. The heterogeneous distribution of the disease is primarily attributed to the characteristics of settlement in specific geographic regions, which have led to the formation of territorial, national, and religious isolates with the accumulation of genetically heterogeneous types in these populations, resulting in an increased genetic burden. [ABSTRACT FROM AUTHOR]

Purpose: To illustrate the importance of systemic evaluation in retinal dystrophies through examples of Alstrom syndrome, Bardet Biedl syndrome, and Refsum disease. Observations: Detailed eye evaluations, including visual acuity, visual field, slit lamp examination, and indirect ophthalmoscopy were performed. Retinal imaging included fundus photography and spectral domain optical coherence tomography (SD-OCT). Functional testing of the retina was done using full field electroretinography (ffERG). In addition, molecular genetic testing was performed using a ciliopathy panel, a retinal dystrophy panel, and whole genome sequencing (WGS).We report three individuals who presented with vision concerns first to ophthalmology, noted to have retinal dystrophy, and then referred to genomic medicine for genetic testing. Additional evaluation led to suspicion of specific groups of systemic disorders and guided appropriate genetic testing. The first individual presented with retinal dystrophy, obesity, and short stature with no reported neurocognitive deficits. Genetic testing included a ciliopathy panel that was negative followed by WGS that identified biallelic variants in ALMS: a novel frame-shift pathogenic variant c.6525dupT (p.Gln2176Serfs*17) and a rare nonsense pathogenic variant c.2035C > T (p.Arg679Ter) consistent with Alstrom syndrome. The second individual presented with retinal dystrophy, central obesity, and mild neurocognitive deficits. A ciliopathy genetic testing panel identified a homozygous pathogenic variant in BBS7: c.389_390del (p.Asn130Thrfs*4), confirming the diagnosis of Bardet Biedl syndrome. The third individual presented with progressive vision loss due to retinitis pigmentosa, anosmia, hearing loss, and shortened metatarsals and digits. Genetic testing identified two variants in PHYH: c.375_375del (p.Glu126Argfs*2) a pathogenic variant and c.536A > G (p.His179Arg), a variant of uncertain significance (VUS), suggestive of Refsum disease. Additional biochemical testing revealed markedly elevated phytanic acid with a low concentration of pristanic acid and normal concentrations of very long-chain fatty acids (C22:0, C24:0, C26:0), a pattern consistent with a diagnosis of Refsum disease. Conclusions and importance: In individuals who present with retinal dystrophy to ophthalmologists, additional systemic manifestations such as sensorineural hearing loss, anosmia, or polydactyly, should be sought and a positive history or examination finding should prompt an immediate referral to a clinical geneticist for additional evaluation and appropriate genetic testing. This facilitates pre-test genetic counseling and allows for more accurate diagnosis, prognosis, and management of affected individuals along with better recurrence risk estimates for family members. Identification of an underlying etiology also enhances the understanding of the pathophysiology of disease and expands the genotypic and phenotypic spectrum. Ultimately, successful recognition of these diseases facilitates development of targeted therapies and surveillance of affected individuals.

Abstract Refsum disease is a rare inherited metabolic disorder arising from a defect in peroxisomal metabolism. Patients lack the functional enzyme phytanoyl‐CoA hydroxylase, resulting in perturbed alpha oxidation of fatty acids. Phytanic acid accumulates in nervous and adipose tissue and leads to several disease phenotypes including early‐onset retinal degeneration, hearing loss, peripheral neuropathy, anosmia, and cerebellar ataxia, among others. Currently, restricting dietary phytanic acid is the only means of altering the chronic sequelae and the disease course. While dietary intervention has been demonstrated to improve peripheral neuropathy, ichthyosis, and ataxia, there have been no reports of improved retinal function in patients with Refsum disease. We describe the case of a 51‐year‐old patient with molecularly and biochemically confirmed Refsum disease who underwent electroretinography before and after beginning a phytanic acid‐restricted diet. His post‐intervention 30 Hz flicker electroretinogram demonstrated significantly improved waveform amplitudes and implicit times, suggesting improved retinal function. Thus, we propose that the possibility exists for some visual recovery in these patients and we highlight the utility of performing standardized electroretinography to assess treatment response in Refsum disease.

Classic Refsum disease (RD) is a rare, autosomal recessively-inherited disorder of peroxisome metabolism due to a defect in the initial step in the alpha oxidation of phytanic acid (PA), a C16 saturated fatty acid with four methyl side groups, which accumulates in plasma and lipid enriched tissues (please see van den Brink and Wanders, Cell Mol Life Sci 63:1752-1765, 2006). It has been proposed that the disease complex in RD is in part due to the high affinity of phytanic acid for retinoid X receptors and peroxisome proliferator-activated receptors. Structurally, epidermal hyperplasia, increased numbers of cornified cell layers, presence of cells with lipid droplets in stratum basale and reduction of granular layer to a single layer have been reported by Blanchet-Bardon et al. (The ichthyoses, SP Medical & Scientific Books, New York, pp 65-69, 1978). However, lamellar body (LB) density and secretion were reportedly normal. We recently examined biopsies from four unrelated patients, using both OsO4 and RuO4 post-fixation to evaluate the barrier lipid structural organization. Although lamellar body density appeared normal, individual organelles often had distorted shape, or had non-lamellar domains interspersed with lamellar structures. Some of the organelles seemed to lack lamellar contents altogether, showing instead uniformly electron-dense contents. In addition, we also observed mitochondrial abnormalities in the nucleated epidermis. Stratum granulosum-stratum corneum junctions also showed co-existence of non-lamellar and lamellar domains, indicative of lipid phase separation. Also, partial detachment or complete absence of corneocyte lipid envelopes (CLE) was seen in the stratum corneum of all RD patients. In conclusion, abnormal LB contents, resulting in defective lamellar bilayers, as well as reduced CLEs, likely lead to impaired barrier function in RD.

Corneocytes in mammalian stratum corneum are surrounded by a monolayer of covalently bound ω-OH-ceramides that form the corneocyte (-bound) lipid envelope (CLE). We review here the structure, composition, and possible functions of this structure, with insights provided by inherited and acquired disorders of lipid metabolism. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Refsum disease (RD) is an inborn error of metabolism that is characterised by a defect in peroxisomal α‐oxidation of the branched‐chain fatty acid phytanic acid. The disorder presents with late‐onset progressive retinitis pigmentosa and polyneuropathy and can be diagnosed biochemically by elevated levels of phytanate in plasma and tissues of patients. To date, no cure exists for RD, but phytanate levels in patients can be reduced by plasmapheresis and a strict diet. In this study, we reconstructed a fibroblast‐specific genome‐scale model based on the recently published, FAD‐curated model, based on Recon3D reconstruction. We used transcriptomics (available via GEO database with identifier GSE138379), metabolomics and proteomics (available via ProteomeXchange with identifier PXD015518) data, which we obtained from healthy controls and RD patient fibroblasts incubated with phytol, a precursor of phytanic acid. Our model correctly represents the metabolism of phytanate and displays fibroblast‐specific metabolic functions. Using this model, we investigated the metabolic phenotype of RD at the genome scale, and we studied the effect of phytanate on cell metabolism. We identified 53 metabolites that were predicted to discriminate between healthy and RD patients, several of which with a link to amino acid metabolism. Ultimately, these insights in metabolic changes may provide leads for pathophysiology and therapy. Databases: Transcriptomics data are available via GEO database with identifier GSE138379, and proteomics data are available via ProteomeXchange with identifier PXD015518. [ABSTRACT FROM AUTHOR]

PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early‐onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot‐Marie‐Tooth disease and Refsum disease. We describe the genotype‐phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome. The genotype was identified using next‐generation sequencing. We examined both patients by means of thorough history taking and clinical examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography to establish a genotype‐phenotype correlation. We identified a novel homozygous point mutation (c.784C > T, p.Arg262*) in the ABHD12 gene. This mutation was detected in both siblings, who had bilateral hearing loss and cataracts, signs of cerebellar ataxia, and neuropathy with a primarily demyelinating pattern in NCS. In one case, retinitis pigmentosa was also evident. As PHARC syndrome is a rare autosomal recessive disorder, our findings highlight the importance of an interdisciplinary diagnostic workup with clinical and molecular genetic testing to avoid a misdiagnosis as Charcot‐Marie‐Tooth disease or Refsum disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the molecular effect of the variant PHYH:c.678+5G>T. This variant has conflicting interpretations in the ClinVar database and a maximum allele frequency of 0.0045 in the South Asian population in gnomAD., Methods: We recruited patients from Moorfields Eye Hospital (London, UK) and Buenos Aires, Argentina, who were diagnosed with retinitis pigmentosa and found to have biallelic variants in PHYH, with at least one being c.678+5G>T. Total RNA was purified from PaxGene RNA-stabilized whole-blood samples, followed by reverse transcription to cDNA, PCR amplification of the canonical PHYH transcript, Oxford Nanopore Technologies library preparation, and single-molecule amplicon sequencing., Results: Four patients provided a blood sample. One patient had isolated retinitis pigmentosa and three had mild extraocular findings. Blood phytanic acid levels were normal in two patients, mildly elevated in one, and markedly high in the fourth. Retinal evaluation showed an intact ellipsoid zone as well as preserved autofluorescence in the macular region in three of the four patients. In all patients, we observed in-frame skipping of exons 5 and 6 in 31.1% to 88.4% of the amplicons and a smaller proportion (0% to 11.3% of amplicons) skipping exon 6 only., Conclusions: We demonstrate a significant effect of PHYH:c.678+5G>T on splicing of the canonical transcript. The in-frame nature of this may be in keeping with a mild presentation and higher prevalence in the general population. These data support the classification of the variant as pathogenic, and patients harboring a biallelic genotype should undergo phytanic acid testing.

Primary iris pigment epithelium cysts involve posterior surface of the iris and can occur at pupillary margin or anterior ciliary body. They may be stationary or progressive and sometimes regress spontaneously. These cyst can occasionally lead to angle-closure glaucoma, plateau iris syndrome and secondary pigment dispersion syndrome. A steadily growing cyst may disturb the vision by covering the visual axis and provoke an increase in intraocular pressure (IOP) or even inflammation if it touches the corneal endothelium. There are multiple management options in complicated situations. We report a case of a 17-year-old girl with unusual complaints of hemeralopia and dark-brown discolouration of pupils in both eyes. On examination, she had multiple pigment epithelial iris cysts at the pupillary margins, which were punctured with Nd:Yag laser, and the response was improvement in vision and hemeralopia without any pigment dispersion or IOP changes. [ABSTRACT FROM AUTHOR]

Zellweger spectrum disorders (ZSD) are rare autosomal recessive inherited metabolic disorders and include severe (Zellweger syndrome) and milder phenotypes [neonatal adrenoleukodystrophy and infantile Refsum disease (IRD)]. ZSD are characterized by impaired peroxisomal functions and lack of peroxisomes detected by electron microscopy (EM). ZSD are caused by mutations in any of the 14 PEX genes. Patients with ZSD commonly demonstrate nonspecific hepatic symptoms within the first year, often without clinical suspicion of ZSD. Thus, recognition of pathologic findings in the liver is critical for the early diagnosis. We herein demonstrate the histologic and ultrastructural features in liver biopsies in the early and advanced phases from a 16-year-old male with IRD. The initial biopsy at 5 months of age showed a lack of peroxisomes by EM, and this finding played a critical role in the early diagnosis. In contrast, the second biopsy at 14 years of age, after long-term diet therapy, demonstrated significant disease progression with near-cirrhotic liver. In addition to lack of peroxisomes, EM revealed abundant trilamellar inclusions within large angulated lysosomes in many of the hepatocytes and Kupffer cells. Mitochondrial abnormalities were identified only in the second biopsy and were mainly identified in damaged cells; thus they were likely nonspecific secondary changes. This is the first report demonstrating histological and ultrastructural features of liver biopsies in the early and advanced phases from a child with ZSD. Trilamellar inclusions are considered to be an ultrastructural hallmark of ZSD, but they may not be apparent in the early phases. [ABSTRACT FROM AUTHOR]

Background: Hereditary peripheral neuropathies constitute a large group of genetic diseases, with an overall prevalence of 1:2500. In recent years, the use of so-called next-generation sequencing (NGS) has led to the identification of many previously unknown involved genes and genetic defects that cause neuropathy. In this article, we review the procedures and utility of genetic evaluation for hereditary neuropathies, while also considering the implications of the fact that causally directed treatment of these disorders is generally unavailable. Methods: This review is based on pertinent publications retrieved by a PubMed search employing the search terms "hereditary neuropathy," "Charcot-Marie-Tooth disease," "hereditary sensory neuropathy," and "hereditary motor neuropathy." Results: With rare exceptions, the diagnostic evaluation for hereditary neuropathies proceeds in stepwise fashion, beginning with the study of individual genes. If this fails to detect any abnormality, NGS analysis, which involves the sequencing of many different genes in parallel and has now become available for routine diagnosis, should be performed early on in the diagnostic work-up. Exome and genome analyses are currently performed only when considered to be indicated in the individual case. Whenever a hereditary neuropathy is suspected, other (including potentially treatable) causes of neuropathy should be ruled out. Mutations in neuropathy-associated genes may also be associated with other clinical entities such as spastic paraplegia or myopathy. Thus, interdisciplinary assessment is necessary. Conclusion: The molecular diagnosis of neuropathies has become much more successful through the use of NGS. Although causally directed treatment approaches still need to be developed, the correct diagnosis puts an end to the often highly stressful search for a cause and enables determination of the risk of disease in other members of the patient's family. [ABSTRACT FROM AUTHOR]

Aims: To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center. Settings and Design: A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present. Results: The frequency of auditory neuropathy spectrum disorder was 1.12%. Sixty percent were found to have neurological involvement. This included cerebral palsy in children, peripheral neuropathy (PN), spinocerebellar ataxia, hereditary motor-sensory neuropathy, spastic paresis, and ponto-bulbar palsy. Neurological lesions did not present simultaneously with hearing loss in most patients. Sixty-six percent of patients with auditory neuropathy spectrum disorder were born of consanguineous marriages. Conclusions: There is a high prevalence of neurological lesions in auditory neuropathy spectrum disorder which has to be kept in mind while evaluating such patients. Follow-up and counselling regarding the appearance of neuropathies is therefore important in such patients. A hereditary etiology is indicated in a majority of cases of auditory neuropathy spectrum disorder.

Refsum Disease is a rare autosomal recessive error of lipid metabolism; onset of symptoms in "classic Refsum disease" or "adult Refsum disease" ranges from age seven months to after age 50 years. The identification of symptoms, that interest all the senses, is essential for the management. We briefly describe a case occasionally diagnosed in adult life and analyzed the main aspects of this rare disease.

Patients suffering from Refsum’s disease show mutations in the enzyme necessary for the degradation of phytanic acid. Accumulation of this tetramethyl-branched fatty acid in inner organs leads to severe neurological and cardiac dysfunctions which can even result in death. Thus, patients with Refsum’s disease have to follow a specific diet resigning foods with high levels of phytanic acid and trans-phytol like products from ruminant animals with a tolerable daily intake (TDI) of ≤ 10 mg/d. We recently reported the occurrence of phytyl fatty acid esters (PFAE, trans-phytol esterified with a fatty acid) in bell pepper with trans-phytol amounts of up to 5.4 mg/100 g fresh weight (FW). In this study we carried out in vitro-digestion experiments of PFAE with artificial digestion fluids. Our results demonstrate that PFAE actually are a source for bioavailable trans-phytol and thus add to the TDI. Eating only one portion of bell pepper (∼150 g) could therefore lead to exploitation of the TDI of up to 81%. Analysis of additional vegetable matrices showed that also rocket salad with up to 4.2 mg/100 g FW trans-phytol bound in PFAE represents a risk-relevant food for patients with Refsum’s disease and should therefore be taken into account. [ABSTRACT FROM AUTHOR]

Phytanic acid is a branched-chain fatty acid, the level of which is elevated in patients with a variety of peroxisomal disorders, including Refsum disease, and Rhizomelic chondrodysplasia punctata type 1 and 5. Elevated levels of both phytanic and pristanic acid are found in patients with Zellweger Spectrum Disorders, and pristanic acid is elevated in patients with α-methylacyl-CoA racemase deficiency. For the diagnosis of peroxisomal disorders, a variety of metabolites can be measured in blood samples from suspected patients, including very long-chain fatty acids, phytanic and pristanic acid. Based on the fact that very long-chain fatty acylcarnitines are elevated in tissues and plasma from patients with certain peroxisomal disorders, we investigated whether phytanoyl- and pristanoyl-carnitine are also present in plasma from patients with different peroxisomal disorders. Our study shows that phytanoyl- and pristanoyl-carnitine are indeed present in plasma samples from patients with different types of peroxisomal disorders, but only when the total plasma levels of their corresponding fatty acids, phytanic acid and pristanic acid, are markedly elevated. We conclude that the measurement of phytanoyl- and pristanoyl-carnitine is not sensitive and specific enough to use these acylcarnitines as conclusive diagnostic markers for peroxisomal disorders. [ABSTRACT FROM AUTHOR]

Phytanic acid is a methyl-branched fatty acid present in the human diet, derived from the enzymatic degradation of phytol and subsequently oxidized by the rumenal microbiota and certain marine organisms. Consequently, phytanic acid is carried into the human body by means of food ingestion, mostly via red meat, dairy products and fatty marine foods. This fatty acid accumulates in people with some peroxisomal disorders and is traditionally related to neurological damage. However, some benefits derived from phytanic acid intake have also been described, such as the prevention of metabolic syndrome or type 2 diabetes. The aim of this work was to conduct an overview of the literature on the phytanic acid content of foods, management of the phytanic content during food production and biochemical mechanisms of phytanic acid metabolism, as well as to assess the evidence for the health benefits and risks of phytanic acid consumption in human health. [ABSTRACT FROM AUTHOR]

Introduction and aim. Hereditary motor neuropathy type VB (HMN5B) is a rare neurological disorder inherited in an autosomal dominant way. It is characterized by weakness and atrophy of the distal muscles, mainly the internal muscles of the hands and of the lower extremities. A mutation of the REEP1 gene is responsible for the onset of the disease. This scientific work describes a clinical case of a nine-year-old boy with HMN, who had an undescribed variant of the REEP1 gene. Description of the case. Parents with a 9-year-old son, previously consulted at the Neurology Clinic because of the neuropathic neuromuscular disorders, appealed to the Genetics Clinic. Due to the recommendation, they did the Trio-WES/ NGS test at the Neurology Clinic. The test result showed a pathogenic mutation of the REEP1 gene of the autosomal dominant sense change type, inherited from the Mother. The gene variant turned out to be unknown. Changes with lower expression of neurological function were found in the woman's Family (Father, Siblings). Based on the Trio-WES/NGS examination and clinical picture, the boy was diagnosed with hereditary distal motor neuropathy type VB. Currently, he is in good contact, the neurological deficit includes an abnormal gait with a drooping right foot. The patient is under neurological care. Conclusion. Hereditary motor neuropathies are a heterogeneous group of conditions, which are included into the group of genetic neuropathies. The REEP1 mutations can be identified in two other diseases: hereditary spastic paraplegia and congenital axonal neuropathy. [ABSTRACT FROM AUTHOR]

Patients with adult Refsum Disease (ARD) have retinitis pigmentosa and thus nyctalopia, anosmia, sensorineural deafness, polyneuropathy, and ataxia. Upon physical examination, patients with ARD have congenital short metacarpals, metatarsals, and cardiac arrhythmias. Manifestations due to the lack of phytanoyl-CoA hydroxylase in peroxisomes needed for alpha-oxidation of phytanic acid lead patients to accumulate phytanic acid in their body tissues. To our knowledge, no consensus for clinical diagnostic criteria for patients with ARD has been published. Our patient had nyctalopia, retinal findings, and visual field results compatible with retinitis pigmentosa. Additionally, the patient had decreased macular thickness and volume in both eyes, the findings being worse in the left eye. The patient had undergone hand surgery due to chronic pain in both hands, as well as his fourth and fifth metatarsal bones were shortened. Interestingly, audiology evaluation showed mild hearing loss in the right ear and mild to moderate hearing loss in the left ear. Inheritance patterns in patients with ARD have been described. Physical examination, phytanic acid evaluation, and genetic studies may all help reach an ARD diagnosis. This is the first report of adult Refsum disease in Puerto Rico., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ramos-Sánchez et al.)